There is circumstantial but impressive evidence that natural cytotoxic (NC) activity is involved in host protection against cancer. This study is designed to analyze the relationship of NC activity to tumorigenicity such that realistic limits can be set on the efficiency of any NC tumor-surveillance system. Although NC and NK (nstural killer) activities have much in common, it has now been established that the NC and NK lytic mechanisms, and how cells avoid lysis by these mechanisms, are fundamentally different and, therefore, what is known about NK activity does not necessarily extend to the NC system. This analysis of NC activity and tumorigenicity is divided into two main sections: (1) the determination of the efficiency of NC activity as a tumor surveillance mechanism. This will determine how significant NC surveillance is as a defense against cancer; and (2) the analysis of how tumors avoid NC lysis in order to grow in vivo. This will provide basic knowledge about the interaction between tumors and host protective mechanisms, and may eventually provide a rational approach for manipulating those interactions. Our research will determine the upper limit of the efficiency of NC activity as a tumor surveillance mechanism by determining the correlation between malignant transformation and NC sensitivity. In addition, research will determine if that correlation is influenced by the tissue origin of the transformed cells or by the type of carcinogen used for transformation, how variants of these cells eacape from NC lysis, and if escape is sufficient to increase tumorigenicity. Recently, an obtained cloned cell line showed it had NC activity. Our research will develop this technology to facilitate not only our experiments but those of others as well. (HF)